Aluminum induces neurofibrillary degeneration that is similar at the light microscopical level to that seen in Alzheimer's Disease. Furthermore, a recent study shows that Al is highly concentrated in neurons containing neurofibrillary tangles in Alzheimer's Disease, suggesting that Al may play an etiological role in this disease. Our overall purpose is to explore the neurochemical effects of chronic Al in animals as a model of Alzheimer's Disease. More particularly, in this application we propoe to examine the effects of Al on several neurotransmitter systems in rabbits. Al will be given intracisternally as a suspension of the powdered metal. This method of administration (in contrast to injections of Al salt solutions) causes a much more slowly progressing 'disease' with neurofibrillary degeneration occurring at different rates in different regions of the CNS. We plan to determine which neurons are affected by measuring the levels of the biosynthetic enzymes of transmitters the neurons utilize in different CNS regions. These data will indicate how the neurochemical changes after Al treatment compare to those seen in Alzheimer's Disease. The enzyme levels will also be measured in the various regions at different times after Al injection to determine the rate at which changes occur and whether the enzyme changes are correlated with the morphological alterations. Neurofibrillary degeneration after Al injection occurs rapidly in ventral horn motor neurons and later a neurogenic muscular atrophy is observed. We plan to determine the levels of choline acetyltransferase in the cholinergic motor neurons in the lumbar ventral horn, sections of sciatic nerve, and in the nerve terminals in the medial gastrocnemius muscle. The results of this study will show if alterations appear first in the cell bodies and progress down the axons with time in a manner coincident with morphological and neurological changes. These studies will enable us to evaluate the neurochemical effects of Al and to consider their relationship to the neurochemical changes in Alzheimer's Disease.